Elimination of fosfomycin during dialysis with the Genius system in septic patients

Abstract To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily...

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Autores principales:	T. Dimski, T. Brandenburger, M. Janczyk, T. Slowinski, C. MacKenzie, D. Kindgen-Milles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8530176a0cd74b80853cf8d0bf37b1a2
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spelling	oai:doaj.org-article:8530176a0cd74b80853cf8d0bf37b1a22021-12-02T14:59:36ZElimination of fosfomycin during dialysis with the Genius system in septic patients10.1038/s41598-021-91423-92045-2322https://doaj.org/article/8530176a0cd74b80853cf8d0bf37b1a22021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91423-9https://doaj.org/toc/2045-2322Abstract To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4–6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.T. DimskiT. BrandenburgerM. JanczykT. SlowinskiC. MacKenzieD. Kindgen-MillesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q T. Dimski T. Brandenburger M. Janczyk T. Slowinski C. MacKenzie D. Kindgen-Milles Elimination of fosfomycin during dialysis with the Genius system in septic patients
description	Abstract To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4–6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.
format	article
author	T. Dimski T. Brandenburger M. Janczyk T. Slowinski C. MacKenzie D. Kindgen-Milles
author_facet	T. Dimski T. Brandenburger M. Janczyk T. Slowinski C. MacKenzie D. Kindgen-Milles
author_sort	T. Dimski
title	Elimination of fosfomycin during dialysis with the Genius system in septic patients
title_short	Elimination of fosfomycin during dialysis with the Genius system in septic patients
title_full	Elimination of fosfomycin during dialysis with the Genius system in septic patients
title_fullStr	Elimination of fosfomycin during dialysis with the Genius system in septic patients
title_full_unstemmed	Elimination of fosfomycin during dialysis with the Genius system in septic patients
title_sort	elimination of fosfomycin during dialysis with the genius system in septic patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8530176a0cd74b80853cf8d0bf37b1a2
work_keys_str_mv	AT tdimski eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients AT tbrandenburger eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients AT mjanczyk eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients AT tslowinski eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients AT cmackenzie eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients AT dkindgenmilles eliminationoffosfomycinduringdialysiswiththegeniussysteminsepticpatients
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Elimination of fosfomycin during dialysis with the Genius system in septic patients

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